The present invention relates to DNA constructs useful to assist in immunization against parvovirus. More particularly, it relates to methods of using such constructs to minimize interference by maternal antibodies.
Various types of disease causing parvovirus are known. See generally B. N. Fields et al., Fields Virology, 3rd Edition, Chapter 69 (1996) (structure of mammalian parvovirus virion). For example, in the 1970's a new viral disease of dogs causing fatal enteritis and/or myocarditis was observed. The virus was named canine parvovirus-2 (CPV-2) in order to distinguish it from an unrelated nonpathogenic canine parvovirus (CPV-1) which had been isolated earlier. See generally 105 Vet. Rec. 156-159 (1979); P. R. Paradiso et al., 62 J. Gen. Virol. 113-125 (1982) (structural characterization of canine parvovirus); A. P. Reed et al., 62 J. Virol. 266-276 (1988) (nucleotide sequence of canine parvovirus-2); S. L. Rhode, 54 J. Virol. 630-633 (1985) (nucleotide sequence of coat protein gene of canine parvovirus-2). The disclosure of these publications, and of all other publications referred to herein are incorporated by reference as if fully set forth herein.
Due to the unusually high morbidity and mortality caused by this virus, substantial efforts have been made to develop vaccines. Vaccines containing feline parvovirus or mink enteritis virus were initially tried. These heterotypic vaccines provided some (albeit insufficient) protective immunity from CPV-2 disease.
Other workers tried to attenuate CPV-2 as well as to make killed CPV-2 vaccines. CPV-2 vaccines, especially the modified live vaccines, provided better protective immunity than the feline and mink vaccines. However, they failed to effectively override maternal antibody, leaving young puppies at risk to infection for weeks or months. This risk period, referred to as the "window of vulnerability", varied among vaccines, but was shown to be as great as 15 weeks in some cases.
Methods were tried to further improve the CPV-2 vaccines, so that the "window of vulnerability" could be shortened. These included 1) liposome encapsulated virus, 2) macrophage engulfed virus, 3) slow release of virus systematically or in the intestinal tract, 4) the use of new heterotypic parvovirus vaccines, 5) vaccinia virus vectored CPV-2 vaccines, 6) vaccines with significantly increased amount of killed or live virus, 7) vaccines with strains of virus that were more immunogenic (e.g. lower number of tissue culture passages, new isolates of CPV-2), and 8) virus-antibody complexes. Most effective was increasing the titer of vaccine virus or increasing the immunogenicity of vaccine virus, which reduced, but did not eliminate the window of vulnerability.
In unrelated work, DNA vaccines for certain viruses other than parvovirus have been developed. In one approach, purified "naked" DNA appears to be taken up and expressed by cells in vivo. A related approach has been the use of a recombinant vector (e.g. a plasmid or a virus such as adenovirus, retrovirus, avipox, herpes or vaccinia virus).
Thus, it can be seen that a need exists for an improved canine parvovirus vaccine.